Joseph disease is an autosomal‐dominant, spinocerebellar degeneration characterized at the biochemical level by elevations in the steady‐state levels of several abundant proteins (H, J, and L) in affected brain areas such as the cerebellar cortex. The increased levels of these proteins could either be a consequence of a relative increase in their de novo synthesis or result from altered rates of proteolysis in degenerating brain cells. These alternatives can be distinguished by comparing the in vitro protein‐synthetic capacities of the messenger ribonucleic acid populations isolated from cerebellar cortex of control subjects and patients with Joseph disease. Protein H (glial fibrillary acidic protein) is synthesized at detectable levels by all messenger ribonucleic acid isolates, and the levels of its translatable messenger ribonucleic acid are reproducibly increased in ribonucleic acids isolated from cerebellar cortex of patients with Joseph disease as compared with those isolated from cerebellar cortex of control subjects. Thus, the increased level of protein H in Joseph disease is a consequence of an increase in its de novo synthesis and is correlated with the increased number of cerebellar glial cells. In contrast to these results, there is no detectable synthesis of proteins J and L by messenger ribonucleic acid populations isolated from cerebellar cortex of either Joseph disease patients or control subjects, suggesting that the increased levels of these proteins in affected cerebellar cortex are a consequence of posttranslational protein modifications.
ASJC Scopus subject areas
- Clinical Neurology